STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation.


Journal Article

Interferon-gamma (IFN-gamma) is required for induction of the human nitric oxide synthase-2 (NOS2) gene in lung epithelium. Although the human NOS2 promoter region contains many cytokine-responsive elements, the molecular basis of induction is only partially understood. Here, the major cis-regulatory elements that control IFN-gamma-inducible NOS2 gene transcription in human lung epithelial cells are identified as composite response elements that bind signal transducer and activator of transcription 1 (STAT-1) and activator protein 1 (AP-1), which is comprised of c-Fos, Fra-2, c-Jun, and JunD. Notably, IFN-gamma activation of the human NOS2 promoter is shown to require functional AP-1 regulatory region(s), suggesting a role for AP-1 activation/binding in the IFN-gamma induction of genes. We show that c-Fos interacts with STAT-1 after IFN-gamma activation and the c-Fos/STAT-1 complex binds to the gamma-activated site (GAS) element in close proximity to AP-1 sites located at 4.9 kb upstream of the transcription start site. Taken together, our findings support a model in which a physical interaction between c-Fos and STAT-1 participates in NOS2 gene transcriptional activation.

Full Text

Cited Authors

  • Xu, W; Comhair, SAA; Zheng, S; Chu, SC; Marks-Konczalik, J; Moss, J; Haque, SJ; Erzurum, SC

Published Date

  • July 2003

Published In

Volume / Issue

  • 285 / 1

Start / End Page

  • L137 - L148

PubMed ID

  • 12788789

Pubmed Central ID

  • 12788789

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

International Standard Serial Number (ISSN)

  • 1040-0605

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00441.2002


  • eng